The prevalence of both hyperprolactinemia and of sexual dysfunction was higher than has been found in previous studies.

Clinical Commentary

Note that because this was a cross-sectional study, cause and effect relationships cannot be determined. Association between two variables does not necessarily mean that one is causing the other.

The prevalence of hyperprolactinemia was very high in this study (71%) and higher than in previous studies. Even though the exact prevalence of hyperprolactinemia will depend on the population studied, clinicians need to appreciate that hyperprolactinemia is very common in persons taking an antipsychotic medication like risperidone or haloperidol (potent D2 receptor blockers).

I think that hyperprolactinemia is under-recognized in clinical settings unless there are obvious clinical effects like galactorrhea or gynecomastia that, of course, occur in a minority of patients.

Hyperprolactinemia is believed to be associated with various long-term risks (e.g., osteoporosis, worsening of prolactin-sensitive tumors).

Patients who realize that, for whatever reason, their sexual functioning is worse when they are on the antipsychotic are at high risk of non-adherence to the medication.

The findings of this study suggest that we should consider checking serum prolactin in persons who develop sexual dysfunction after starting an antipsychotic.

If hyperprolactinemia is present, we should consider switching to an antipsychotic with a lower potential for causing hyperprolactinemia or, if clinically indicated, adding a medication that may reverse the hyperprolactinemia.

There is continuous interest in alternatives to stimulant medication for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD), especially in children and adolescents.

One of these is EEG neurofeedback. Children with ADHD are believed to have more theta (4 to 7 Hz) activity and less beta (13 to 20 Hz) activity. Greater beta activity is associated with alertness. EEG neurofeedback provides visual or auditory feedback about the theta/beta ratio and this feedback helps children learn to maintain greater alertness.

Of three previous randomized, controlled trials comparing neurofeedback to medication, two trials reported neurofeedback and medication to be equally efficacious and one reported that medication was more efficacious than neurofeedback. Thus, the question of whether neurofeedback is as efficacious as medication remained uncertain.

This study, therefore, aimed to compare the efficacy of EEG neurofeedback versus methylphenidate

Methods

This was a randomized, controlled trial.

The 112 participants were children aged 7 to 13 years who had a diagnosis of ADHD.

The three treatment groups were methylphenidate, EEG neurofeedback, and physical exercise.

The methylphenidate was titrated up to the optimal, individualized dose for each patient. Short-acting methylphenidate 5 to 20 mg twice daily (i.e., 10 to 40 mg/day) was given at breakfast and lunch. Each of the doses was tried for a week and the “optimal” dose was identified and then continued for the rest of the duration of the study.

The EEG neurofeedback was comprised of theta/beta training on the vertex of the head.

The physical exercises were of moderate to vigorous intensity. Physical exercise was used as a plausible control intervention to control for nonspecific effects like increased monitoring and attention to the child. The number (about 30 sessions) and duration of the EEG neurofeedback and physical exercise sessions were approximately equal.

The children were evaluated through parent and teacher ratings using two questionnaires:

The Strengths and Difficulties Questionnaire (SDQ), and

The Strengths and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN)

Results

Parents reported improvement on both the questionnaires for children in all three of the treatment groups.

Only in looking specifically at the SWAN Inattention scale, as reported by the parents, children who received methylphenidate had statistically significantly more improvement than children who received either EEG neurofeedback or physical exercise.

On the questionnaires filled out by the teachers, on the other hand, the ADHD symptoms improved on all the measures in children receiving methylphenidate but not in children receiving EEG neurofeedback or physical exercise.

The authors speculated that the reason for the discrepancy in parents’ and teachers’ ratings may be because the parents needed to be actively involved in the neurofeedback or physical exercise. The teachers had no active role in this. Therefore, the parents were more likely to be subject to an expectation bias, i.e., expecting the treatment to work.

Conclusions

For ADHD symptoms in children, individualized treatment with methylphenidate was more efficacious compared to EEG neurofeedback or physical exercise.

Clinical Commentary

Alternatives to medication, such as neurofeedback, are understandingly appealing to parents. However, clinicians making treatment recommendations should be clear that despite the availability of various other interventions, stimulant treatment remains the most effective treatment for symptoms of ADHD in children.

It is, of course, possible that EEG neurofeedback or physical exercise when added to stimulant medication may have additional benefits though this should not be assumed to be true.

Hypersalivation is a common and distressing adverse effect of treatment with clozapine. It often leads to discontinuation of treatment.

While some treatment options exist, they are not effective in all patients.

Metoclopramide is a dopamine D2 antagonist, 5-HT3 antagonist, and 5-HT4 agonist that is used for the treatment of nausea/vomiting.

Metoclopramide causes dry mouth as an adverse effect in about 10% of patients.

This clinical trial aimed to evaluate the efficacy of metoclopramide for the treatment of clozapine-induced hypersalivation.

Methods

This was a randomized, double-blind, placebo-controlled clinical trial.

58 patients were enrolled who had the following characteristics:

1. Diagnosis of schizophrenia or schizoaffective disorder

2. Being treated with clozapine for at least two months

3. Significant nocturnal hypersalivation as defined on a rating scale.

The subjects were randomized to receive either metoclopramide or placebo for 3 weeks.

Doses of other medications were kept constant during the study.

Metoclopramide was started at 10 mg/day at 8 pm. If needed, after one week, the dose was increased to 10 mg at 8 am and 8 pm. After another week, if needed, the dose was increased to 10 mg three times a day. Thus, the daily dose was 10 to 30 mg/day.

Results

Using rating scales for hypersalivation and for drooling, metoclopramide was statistically significantly more efficacious than placebo.

The patients treated with metoclopramide were judged to be substantially improved by the investigators who were blinded to the treatment the patients were receiving.

67% of patients who received metoclopramide versus 29% of patients who received placebo had either a significant decrease or complete resolution of the hypersalivation. That is a 38% difference, which is huge.

No adverse effects were reported.

Conclusions

Metoclopramide was an effective and well-tolerated treatment for clozapine-induced hypersalivation.

Clinical Commentary

In patients treated with clozapine, hypersalivation should be treated and not ignored, not only to reduce personal distress but also to reduce discontinuation of treatment.

We must keep in mind that clozapine is a very important medication given its unique role in treating schizophrenia that has not responded to other antipsychotic medications. Given the lack of adequate alternatives to clozapine, it is particularly important to try to keep the patient on this medication.

GME Research Review is a monthly newsletter edited by Rajnish Mago, MD, who is author of "The Latest Antidepressants" and "Side Effects of Psychiatric Medications: Prevention, Assessment, and Management." Dr. Mago selects, summarizes, and provides a clinical commentary on the latest published research in psychiatry.

We are always carefully evaluating which research papers to discuss in GME Research Review. Have come across a research paper published in the last 6 months that you thought is clinically relevant? Do you want me to analyze it for you and for the benefit of others? Please email Dr. Mago the citation at [email protected].

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